The last trimester and early postnatal months of human development are characterized by rapid development of the retina and visual cortex. While the postnatal improvement of visual function and sensitivity to disruption by abnormal early visual environments have been extensively studied, the role of other environmental variables in human visual development has only recently been addressed. The present study is designed to evaluate the longterm effects of dietary omega-3 and omega-6 long-chain polyunsaturated fatty acid (LCPUFA) supply on retinal and brain development in low birthweight preterm infants and in fullterm infants. There is a high concentration of omega-3 and omega-6 LCPUFAs in electrically active membranes, particularly in brain synaptic terminals and in retinal photoreceptors. Since mammals are unable to synthesize essential fatty acids (EFAs), optimal retinal and neural development depend on placental transfer in utero and on dietary sources postnatally. Moreover, neonates may have immaturities which limit their ability to elongate/desaturate parent EFAs to form LCPUFAs. Prospective studies of infants randomized to standard infant formula or to experimental formulas containing docosahexaenoic acid (DHA; 22:6 omega- 3) and DHA plus arachidonic acid (AA; 20:4 omega-6) will evaluate the effects of LCPUFA supply on retinal and brain maturation by means of electroretinograms, pattern-reversal visual evoked potentials, forced- choice preferential looking, electroencephalographic studies of the sleep-wake cycle, and Bayley and Fagan tests. Fatty acid profiles in red blood cells will be used as an index of LCPUFA status in neural tissue and to verify compliance with diet. In vitro studies will examine the effects of LCPUFA supplementation on the developing fetal human retina and will provide new information on mechanisms by which DHA and AA influence biological and morphological characteristics. The longterm goal of this project is to define nutritional requirements for optimal retinal and cortical development of the human infant. The specific projects proposed here will help to characterize the role of LCPUFAs in promoting retinal and cortical development and will be crucial in determining whether there is a need for LCPUFA supplementation of preterm and/or term infant formula.